叶酸聚谷氨酸合成酶基因rs10760502G>A多态性与儿童急性B淋巴细胞白血病预后及甲氨蝶呤毒副反应的相关性分析  

Correlation Analysis of FPGS rs10760502G>A Polymorphism with Prognosis and MTX-related Toxicity in Pediatric B-cell Acute Lymphoblastic Leukemia

作　　者：刘曙光[1] 高超[1] 李志刚[1] 李伟京[1] 崔蕾[1] 赵晓曦[1] 郑胡镛[1] 吴敏媛[1] 张瑞东[1] 

机构地区：[1]首都医科大学附属北京儿童医院血液肿瘤中心、儿童血液病与肿瘤分子分型北京市重点实验室、教育部儿科重大疾病重点实验室、儿科学国家重点学科,北京100045

出　　处：《中国实验血液学杂志》2014年第2期291-297,共7页Journal of Experimental Hematology

基　　金：首都医科大学基础-临床科研合作基金(13JL72);北京市自然科学基金项目北京市教育委员会科技计划重点项目(KZ201210025031);"重大新药创制"科技重大专项项目(2011ZX09302-007-01)

摘　　要：本研究旨在探讨叶酸聚谷氨酸合成酶(FPGS)基因中rs10760502G>A多态性与儿童急性B淋巴细胞白血病(B-ALL)预后及甲氨蝶呤(MTX)毒副反应的相关性。采用Sequenom MassARRAY时间飞行质谱系统检测rs10760502基因型。实验数据采用x2检验、Kaplan-Meier生存分析、Cox回归分析等统计方法处理。结果表明:A等位基因携带者(GA+AA)无复发生存率(RFS,log-rank:P=0.004)及无事件生存率(EFS,log-rank:P=0.022)显著低于GG等位基因型携带者。多因素Cox回归分析显示,A等位基因是RFS[hazard ratio(HR),20.173;95%CI,2.535-160.545;P=0.005]及EFS(HR,8.133;95%CI,1.718-38.512;P=0.008)的独立不良预后因素。rs10760502多态与MTX毒副反应间未见相关性。结论:FPGS rs10760502G>A多态性位点可能作为BALL患儿的独立预后因素。This study was aimed to explore the relation between folylpolyglutamate synthetase （FPGS） rs10760502 polymorphism and prognosis and methotrexate （MTX）-related toxicities in pediatric B-cell acute lymphoblastic leukemia （B-ALL）. Sequenom MassARRAY was used to genotype rs10760502. The χ2 test, Kaplan-Meier method and Cox regression models were used to analyze the data. The results indicated that A allele carriers （ GA ＋ AA） had poor relapse free survival （ RFS, log-rank： P = 0. 004） and event free survival （ EFS, log-rank： P = 0. 022 ） compared with the GG genotype carders. Multivariate Cox-regression analysis results showed that A allele is an independent prognosis factor for poor RFS Ehazard ratio （ HR）, 20. 173 ; 95% CI, 2. 535 - 160. 545 ; P = 0. 005 ] and EFS （ HR, 8. 133 ; 95% CI, 1. 718 -38. 512; P = 0. 008 ）. No relationship was found between any MTX toxicity and rs10760502 polymorphism. It is concluded that FPGS rs10760502G 〉 A polymorphism may affect the treatment outcome of B-ALL patients.

关 键 词：叶酸聚谷氨酸合成酶 甲氨蝶呤 急性淋巴细胞白血病 

分 类 号：R733.71[医药卫生—肿瘤] R979.1[医药卫生—临床医学]